The diuretic, metolazone, is a sulfonamide derivative and chemically resembles the thiazide group of diuretics. Its chemical name is 2-methyl-3-o-tolyl-6-sulfamyl-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone and it is described in U.S. Pat. No. 3,360,518 which is incorporated by reference. One side effect of metolazone is hypokalemia or abnormally low potassium levels in the blood. Triamterene, 2,4,7-triamino-6-phenylpteridine, is a pyrazine derivative which promotes the reabsorption of potassium while inhibiting sodium reabsorption in the distal tubule. Triamterene is described in U.S. Pat. No. 3,081,230 which is incorporated by reference. Triamterene also has a mild diuretic action of its own and when used with other common diurectics has been reported to have a synergistic effect in treating persons for hypertension. The concurrent administration of metolazone and triamterene to correct potassium losses resulting from the use of metolazone alone has been recommended in the literature, for example, Onesti "When Hypertension is Complicated", Drug Therapy, pp. 66-78 (1975). Zeller, "Efficacy of Metolazone in the Long-Term Treatment of Hypertensive Patients", Current Therapeutic Research, Vol. 29. No. 4 pp. 45-1 to 45-8 (1981), reported that triamterene had no significant effect on the reduction of potassium caused by metolazone use. However, Hollifield, "Some Biochemical Consequences of Diuretic Therapy of Low Renin Essential Hypertension", from "Systemic Effects of Antihypertensive Agents", M. P. Sambhi, Editor, Symposia Specialists, pp. 140 and 141 (1976) reports that triamterene administered along with metolazone blocked the kaliuresis induced by metolazone.
A common problem associated with solid dosage forms of metolazone and triamterene is their poor dissolution characteristics. I have found that a combination tablet containing a mixture of metolazone and triamterene is effective in the treatment of hypertension while reducing the hypokalemia which can result from the use of metolazone alone. The combination tablet unexpectedly possesses enhanced dissolution properties with respect to both metolazone and triamterene.